Proposed work will center on investgations of the role of herpes simplex virus (HSV) thymidine kinase (TK) expression in acute and latent infection of the trigeminal ganglion. We have demonstrated with a number of HSV strains that TK expression is necessary although probably not sufficient for the establishment of ganglionic infection. In vivo complementation studies will be performed to further investigate the role of TK expression. In preliminary studies we have evidence that TK-plus HSV complemented TK-minus HSV and also that some TK-minus-TK-minus mixtures complemented. These studies done during the acute period of ganglionic infection will be extended. In addition, although complementation seems to permit TK-minus HSV replication in ganglionic tissue, it is not evident whether the TK-minus HSV replicated may then establish a latent infection. This will be investigated in long-term experiments in mice inoculated with several TK-plus-TK-minus and TK-minus-TK-minus mixtures.